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Research Articles

Below you will find a database containing Research Articles on the Angelman Syndrome/

We try to keep it as much up to date as possible. This is done with a team of people who search the internet or contact researches to ask for permission to post their articles. The articles are placed in their original language, most of the time English.

We identified in a large Tunisian pedigree a novel UBE3A frameshift mutation in exon 16 coding region, and we expect that the resulting UBE3A truncated protein in our patients is non-functional since the mutation implies the catalytic region of the enzyme. The family includes 14 affected patients born from four sisters. This mutation was found in all surviving affected individuals and their mothers pointing out the importance of genetic counseling possibility in Angelman syndrome (AS). All patients had severe mental retardation with epilepsy and microcephaly. Minor clinical expression variation was observed among the investigated patients. The severity of clinical expression is related to the detected molecular variation: deletion of 15 bp and insertion of 7 bp. These results are concordant with the gene expression observed in previously reported individuals with AS and truncated UBE3A protein.

The neurodevelopmental disorder Angelman syndrome is most frequently causedby deletion of the maternally-derived chromosome 15q11-q13 region, which includes notonly the causative UBE3A gene, but also the beta3-alpha 5-gamma3 GABAA receptor subunit genecluster. GABAergic dysfunction has been hypothesized to contribute to the occurrence ofepilepsy and cognitive and behavioral impairments in this condition. In the present study,analysis of GABAA receptor subunit expression and pharmacology was performed incerebral cortex from four subjects with Angelman syndrome and compared to that fromcontrol tissue. The membrane fraction of frozen postmortem neocortical tissue wasisolated and subjected to quantitative Western blot analysis. The ratios of beta3/beta2 and alpha 5/alpha 1subunit protein expression in Angelman syndrome cortex were significantly decreasedwhen compared with controls. An additional membrane fraction was injected intoXenopus oocytes, resulting in incorporation of the brain membrane vesicles with theirassociated receptors into the oocyte cellular membrane. Two-electrode voltage clampanalysis of GABAA receptor currents was then performed. Studies of GABAA receptorpharmacology in Angelman syndrome cortex revealed increased current enhancement bythe alpha 1-selective benzodiazepine site agonist zolpidem and by the barbituratephenobarbital, while sensitivity to current inhibition by zinc was decreased. GABAAreceptor affinity and modulation by neurosteroids were unchanged. This shift in GABAAreceptor subunit expression and pharmacology in Angelman syndrome is consistent withimpaired extrasynaptic but intact to augmented synaptic cortical GABAergic inhibition,which could contribute to the epileptic, behavioral, and cognitive phenotypes of thedisorder.

Angelman syndrome is a neurodevelopmental disorder caused by mutations in the maternally inherited UBE3A gene, which encodes a ubiquitin ligase. Greer et al. (2010) now identify a UBE3A substrate called Arc that promotes endocytosis of neuronal AMPA receptors, providing insight into synaptic defects that may underlie the cognitive deficits in Angelman syndrome. Angelman syndrome is a neurodevelopmental disorder caused by mutations in the maternallyinherited UBE3A gene, which encodes a ubiquitin ligase. Greer et al. (2010) now identify a UBE3Asubstrate called Arc that promotes endocytosis of neuronal AMPA receptors, providing insight intosynaptic defects that may underlie the cognitive deficits in Angelman syndrome.